The development of a flexible sensing platform for biomedical device and diagnostic applications is critical to advancing current diagnostic and analytical techniques used in the healthcare field. Electronic fabrics or smart textiles are at a forefront of biomedical research for a variety of ambulatory, diagnostic, and therapeutic devices. Two examples where such a sensing platform would be beneficial are in cystic fibrosis diagnosis and monitoring stump-socket conditions for amputee patients. The sensing platform of the present invention could also be extended to other biomedical applications such as wound healing.
Cystic fibrosis (CF) is a life-threatening genetic disease that attacks the lungs, pancreas, liver, and intestines and affects the lives of over 26,000 Americans, including nearly 900 newly diagnosed cases in 2010. CF is prevalent among Caucasians, but has been found to affect all racial and ethnic groups. The Cystic Fibrosis Foundation estimates that one in 3,500 newborns have the disease, which is not diagnosed until a median age of 5 months old. The disease causes a thick, sticky mucus to build up in some organs and organ systems, causing complications and even possibly organ failure or death. This disorder does not discriminate, as it can be passed to both males and females with approximately a 50:50 distribution. The gene presents with over 1,200 different mutations, many of which are specific to individual family lines. This makes identifying and diagnosing both affected individuals, as well as carriers of the disease, extremely important in tracing the dysfunctional genotypes. CF patients have an abnormally high transport of sodium and chloride ions across the epithelium and therefore the disease is most commonly diagnosed by sweat electrolyte testing, which the Cystic Fibrosis Foundation recommends as the standard of CF diagnosis in children.
Suspected descriptions of CF have been documented since the late 1500's. However, the disease was not specifically identified until the late 1930's, and the sweat electrolyte diagnostic test was implemented as late as the 1950's. The identification of the CF gene did not occur until 1989, but research into its malfunction has dramatically increased since that time. This brings us to the current state of CF treatment and research, that has evolved considerably with the exception of diagnostic testing (the sweat test), which has not changed significantly for over sixty years.
The Cystic Fibrosis Foundation, as well as other medical sources, emphasizes that early diagnosis is critical in the success of treating the disease and prolonging the life expectancy of patients, making a quick and accurate diagnosis of the utmost importance. In the US, only about 70% of all cystic fibrosis patients are diagnosed before their first birthday, and only about 90% are diagnosed before their eighth birthday. These statistics are surprisingly lower throughout the world, where some affected individuals go their entire life undiagnosed.
The sweat test, which may also be referred to as the iontophoretic sweat test or sweat electrolyte test, is the current diagnostic protocol for cystic fibrosis and is described by LeGrys et al. in The Journal of Pediatrics, vol. 151, no. 1, pp. 85-89, July, 2007. This test is performed by applying a colorless odorless chemical (pilocarpine), that induces sweating, to the arm, leg, or foot, and stimulating the area via electrode. The sweat is then collected with a gauze or filter, and sent to a hospital laboratory, where either the sodium ion or chloride ion level can be measured. The accuracy of this test greatly depends on the skill of the clinician administering the collection, and the quality of the lab equipment. Furthermore, the risk of contamination is always a factor when a sample has to be transported or handled, and should be avoided if at all possible, as a false negative can be detrimental to the treatment process.
The entire collection procedure takes about an hour and requires a large sample size, for example about 50 g of sweat, which is especially difficult to collect from a newborn. The time required for the laboratory analysis is variable depending on the location of the collection and instrumentation of the lab. However, reliable sweat levels are present after five minutes. If the sodium levels in the patients sweat were read after this short five minute period, the diagnosis could be concluded hours, or even days, earlier than with the present methods. It has been shown that the sweat testing process of a suspected newborn is a time of immoderate anxiety for parents and other family members. A straightforward way of reducing stress to the family would be to promptly perform the test and obtain the results as soon as possible. Therefore, there is a need for accurate testing to be performed in real-time.
Current techniques are not adequate; analytical techniques used in ion quantification include atomic absorption spectrophotometry [AAS], inductively coupled plasma-atomic emission spectroscopy [ICP-AES], and ion chromatography, among others. Sweat conductivity tests have also been developed, but are not approved by the U.S. Food & Drug Administration [FDA], and are not expected to become diagnostic protocol. Current sensor technologies developed for ion quantification involve rigid electrodes, and/or the use of optical techniques.
Temperature detection close to the skin is normally an easily completed task using a thermometer, but it becomes more difficult when trying to detect conditions close to the skin for purposes of monitoring or controlling factors, i.e. temperature and humidity, related to the enclosed environment around the detection area. It becomes more difficult due in part to the desire for accurate measurements while maintaining comfort, especially for prolonged use or wear. The majority of temperature detectors are made from rigid materials that would create pressure points against the skin in load-bearing situations. For example, imagine temperature changes need to be detected inside the prosthetic socket of a lower limb amputee to either control a cooling system for their prosthetic or to model the patient's daily activity over a prolonged period of time. Now, the prosthetic is designed to fit snug against the patient's residual limb for proper care and usage. Having a small rigid detector constantly inside the prosthetic socket would be like walking around with a grain of sand in a shoe.
Previously, flexible temperature sensor arrays have been used to detect and record temperature through integrated circuits, which are metal thin-film interconnects and traces sandwiched between semi rigid polymer sheets. Some of the devices use a conductive polymer composite as the sensing material, while others use thin metal films in various configurations for different type of detection, i.e. temperature and strain. Others have developed temperature sensitive fibers using polymer composites or carbon nanotubes for small site and stationary electronic applications. These devices work well for electronic skins, robotics, and electronics applications, but would create pressure points and uncomfortable regions for detecting temperature changes at or close to the human dermis. A flexible temperature sensitive fabric would facilitate detecting temperature changes close to the skin for extraneous activities, or instances where pressure may be applied to the detecting surface.
The most current estimate states there are approximately 1 in 190 persons living in the United States with major limb-loss and the rate of amputations increases each year. This necessitates an importance for understanding both quality of life rated (QOLR) issues and options to remediate prevalent problems. One major issue for amputees using socket style prosthesis is the combination of heat and sweat in the socket. Most amputees wear their prosthetic for eight or more hours a day. This is troublesome for a residual limb, because the socket can become hot and humid during even just regular use and can cause a variety of dermatological conditions if proper care is not taken. The major contributors to heat and sweat inside the socket are personal activity, and socket and liner materials of construction. The materials used in socket and liner construction negatively affects the socket environment by inhibiting heat transfer away from the residual limb and just ten minutes of walking can increase the average residual limb temperature by 1.7° C. A reduction in heat transfer causes sweat inside the socket, which can create a moist, abrasive environment against the skin. Currently, there are no systems able to monitor temperature and sweat conditions at the stump-socket interface.
The present invention provides for a quantitative sodium ion sensor for use as a diagnostic tool. The present invention also fulfills the need for a soft, resistive fabric to detect temperature changes at or close to the human skin by also providing for a sensing platform able to determine temperature and sweat conditions at the stump-socket interface. Further, the present invention provides for such diagnostics and testing inexpensively, yet very accurately. The present invention provides for biosensors having wide applicability. Besides CF and stump-socket interface applications, the present invention may be advantageously used for non-limiting examples such as monitoring diabetic feet as well as military applications such as monitoring dehydration during combat or various applications to aid pilots. This device could also be extended to the diagnosis of common diabetic neurological complications, such as autonomic neuropathy or peripheral neuropathy, as these are accompanied with symptoms affecting sweat regulation.